Abstract

Central nervous system (CNS) tumors are the second most common cause of cancer in children when incidence rates of cancer are estimated according to the Indian population dynamics based on 2011 consensus. As per the estimates, CNS tumors account for 20.1%-of cancer burden in children aged between 0 and 14 years and 16.8%-when 0 to 19 years age group is considered. The most common pediatric brain tumors are astrocytoma and medulloblastoma followed by other embryonal tumors, craniopharyngioma, and ependymal tumors. The incidence of CNS tumors in children from India is similar to the western high-income countries, other than slightly higher incidence of craniopharyngioma in Indian children.

Introduction

Central nervous system (CNS) tumors are the second most common cause of cancer in children when incidence rates of cancer are estimated according to the Indian population dynamics based on 2011 consensus. As per the estimates, CNS tumors account for 20.1%-of cancer burden in children aged between 0 and 14 years and 16.8%-when 0 to 19 years age group is considered.[1] The most common pediatric brain tumors are astrocytoma and medulloblastoma followed by other embryonal tumors, craniopharyngioma (CP), and ependymal tumors.[2] The incidence of CNS tumors in children from India is similar to the western high-income countries (HIC), other than slightly higher incidence of CP in Indian children.[2] [3]

Symptoms/Presentation

Central nervous system (CNS) tumors are the most common solid tumors in children. The worldwide incidence of pediatric CNS tumors varies from 1.12 to 5.14 per 1,00,000 individuals.[4] The peak age for pediatric CNS tumors is less than 5 years after which the incidence of CNS tumors is less till up to 15 years of age after which the incidence rates are almost like adults.[5] In the Indian population, the age-adjusted rates for the incidence of childhood CNS tumors range from 6.6 to 19.8 per million for boys and 3.0 to 16.0 per million for girls.[6]

The common presenting symptoms of pediatric CNS tumors are headache, vomiting, seizures, or cranial nerve deficits, which are quite nonspecific. This can lead to delayed or missed diagnosis.

Prognosis/Survival

The data to evaluate prognosis or study survival statistics in children with CNS tumors in India is scarce. The overall incidence of pediatric CNS tumors in India is low compared to the HIC, probably due to missed diagnosis or failure to recognize symptoms attributable to CNS tumors. As per a study from South India with data on institutional follow-up for pediatric CNS tumors, the mortality was found to be approximately 15.3%-with significant treatment drop-out.[7] The 5-year survival data from a systematic review of worldwide literature from 1980 to 2009 concludes variability in survival statistics over the decades depending on tumor grade. There was significant improvement in survival for embryonal tumors (37%-in 1980 to 60%-in 2009), whereas the survival for astrocytoma changed very little (78%-in 1982 to 89%-in 2009) over the years.[8]

Role of Imaging

Magnetic resonance imaging (MRI) is the modality of choice for initial baseline assessment of a brain tumor and for follow-up imaging to assess for treatment response. Computed tomographic (CT) scan can be useful for certain cases when the intracranial lesion is heavily calcified (e.g., CP) and for tumors near the skull base or involving the skull vault to assess for bony changes. However, CT scan is usually always performed in conjunction with an MRI for complete assessment.

Across India, there are multiple cancer treatment hospitals, either managed by the government or run privately. The various institutions have a variety of MRI/CT scanners from different vendors with the MRI field magnet strength ranging from 0.5T to 3T. Also, many scans are performed at standalone private diagnostic centers and images are provided as hard prints on films. Some of the other challenges in pediatric brain/spine imaging are lack of anesthetic support or lack of expertise in reporting those scans. This greatly limits the prospect of multicenter study trials due to the inhomogeneity in scan planning and acquisition. It is a pressing priority to have a standardized imaging protocol across various institutions to be able to include more patients in pediatric CNS tumor trials and improve treatment outcomes.

The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee have recently published recommendations for image acquisition and have clearly defined response criteria for the pediatric brain tumors.[9] [10] [11] [12] Based on these recommendations, the European Society of Paediatric Oncology Brain Tumour imaging Working Group has provided their own recommendations for pediatric brain tumor imaging that consists of minimal essential/mandatory sequences and additional sequences including advanced imaging methods that can be performed as per local imaging policy.[13] Applying these recommendations to the Indian scenario poses unique challenges as discussed above and thus we have formed imaging guidelines that will most suite to the Indian subcontinent in terms of utilizing the limited imaging capacity and improvise on the reporting standards with a clear guideline for timing the scans. We have also included templates for reporting formats to achieve minimal variability in reporting standards and facilitate wider acceptance of cases for future pediatric CNS tumor trials.

Pediatric CNS Tumor Grade on Imaging

The conventional T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) sequences give a good overview of the extent as well as the characteristics of the lesion with information on perilesional edema and mass effect on surrounding structures. The highly cellular lesions cause T2 shortening and generally appear iso to hypointense on T2W images. FLAIR signal changes combined with diffusion-weighted imaging/apparent diffusion coefficient (DWI/ADC) maps give information on perilesional edema versus tumor infiltration. Some low-grade gliomas (LGGs) have a bubbly appearance on imaging with a FLAIR hyperintense rim (highly suggestive of a dysembryoplastic neuroepithelial tumour [DNET]). Calcifications can be seen in low-grade tumors like pilocytic astrocytoma (PA), intermediate grade lesions like supratentorial ependymomas (EP) and in high-grade tumors like atypical teratoid rhabdoid tumor (ATRT). However, when the lesion is largely calcified with no associated enhancing component or abnormal diffusion changes, it is usually a low-grade lesion. T1W imaging is helpful specially to look for hemorrhage or calcification in the lesion as gradient or susceptibility imaging sequences are not generally part of tumor imaging protocol. The other important utility of precontrast T1W imaging is on the postoperative scan to distinguish postoperative hemorrhage from abnormal postcontrast enhancement along the resection margins that can indicate residual disease.

Postcontrast enhancement at baseline imaging in a pediatric CNS tumor does not play as big a role as it does for adult CNS tumors, as it does not reflect tumor grade in pediatric cases. However, postcontrast enhancement is particularly important in some metastasizing low-grade tumors (e.g., 5–10%-of PA can metastasize) that only show enhancement and this can be the only feature on imaging to pick up smaller lesions or leptomeningeal spread.[14] Enhancement plays an important role for tumor follow-up (f/u) for the lesions that showed enhancement at baseline imaging, to map the tumor extent or recurrence on f/u imaging (e.g., PA) and also for nonenhancing lesions at baseline that show abnormal postcontrast enhancement on f/u suggesting progression or change in lesion grade (e.g., World Health Organization [WHO] grade I diffuse astrocytoma MYB or MYBL1 altered).[14] Postcontrast imaging can also help to assess tumor response as LGG show significantly reduced enhancement after treatment with MEK inhibitors or BRAF inhibitors; however, this should be weighed with tumor size measurement on T2W/FLAIR imaging.[9]

DWI with ADC maps is one of the most important sequences for pediatric CNS tumor grading. Tumors can be graded by obtaining ADC value of the lesion by drawing a region of interest on the ADC map where the lower ADC values correspond to higher grade and cellularity. Some higher grade lesions do not show postcontrast enhancement and in such cases a lower ADC value can help assess for high tumor cellularity as well as for nonenhancing metastasis, a classic example being leptomeningeal and spinal metastasis in grade 4 medulloblastoma showing a contrast enhancement-DWI mismatch.[15] Diffusion has a crucial role in determining progression for the nonenhancing tumors on antiangiogenic therapy and to distinguish recurrence from pseudo-progression in high-grade tumors.[16] [17]

Pediatric Brain Tumor Types

The pediatric brain tumors have several classification systems that are based on histology, molecular features, and/or site of origin of the lesion. Approximately two-third of CNS tumors in adults are supratentorial, whereas, in children approximately two-third of CNS tumors are infratentorial. Some genetic syndromes like neurofibromatosis (NF) type 1 and 2, tuberous sclerosis and Li-Fraumeni syndrome show propensity to develop brain tumors.

The most recent update by the new WHO 2021 classification of CNS tumors (WHO CNS 5) have introduced and merged many categories form the previous classification. The WHO CNS5 have classified brain tumors mainly based on the combination of histological and molecular features. The common pediatric infratentorial tumors are medulloblastoma, cerebellar astrocytoma, EP, brain stem diffuse midline glioma (including diffuse intrinsic pontine glioma [DIPG]), and ATRT. The common pediatric supratentorial tumors are LGG, high-grade gliomas (HGG), embryonal tumors, pituitary tumors, and pineal tumors.

Low-Grade Gliomas and Other Low-Grade Tumors (WHO grade I/11)

LGG are tumors of glial origin and are WHO grade I and II tumors. LGG are the most common pediatric CNS tumors accounting for nearly 40 to 50%-of all CNS tumors.[18] In the WHO CNS5 classification, pediatric LGGs are classified as circumscribed, diffuse, and glioneuronal tumors. The LGG commonly arise in the hypothalamic-chiasmatic region (40%), cerebellum (25%), and cerebral hemispheres (17%), with a small proportion occurring in the brain stem (9%).[18] [19] Optic pathway lesions are generally more diffuse and quite extensive in children often involving the hypothalamic–chiasmatic axis when sporadic. When associated with a cancer predisposition syndrome, the LGG are classically seen involving the optic pathway and brain stem (10–15%-of NF type 1 patients).[20] PA is the most common LGG (∼16%).[21] The other less common low-grade lesions are diffuse astrocytoma, pilomyxoid astrocytoma, pleomorphic xanthoastrocytoma, and DNET. The recent 2021 WHO classification of CNS tumors have added a new category for diffuse LGGs with four entities under this category: diffuse astrocytoma, MYB- or MYBL1-altered; angiocentric glioma; polymorphous low-grade neuroepithelial tumor of the young; and diffuse LGG, MAPK pathway-altered.[22]

High-Grade Gliomas and Embryonal Tumors

HGG encompass a variety of WHO grade III and IV glial tumors and the second most common pediatric CNS tumors. The common HGG gliomas are anaplastic astrocytoma (WHO III), glioblastoma multiforme (WHO IV), and diffuse midline gliomas. The new diffuse pediatric HGG category in the new 2021 WHO CNS tumor classification has four entities under it: diffuse midline glioma (H3 K27-altered), diffuse hemispheric glioma (H3 G34-mutant), diffuse pediatric-type HGG (H3-wild-type and IDH-wild-type), and infant-type hemispheric glioma.[22]

Embryonal tumors are one of the most common high-grade CNS lesions in children and medulloblastoma is the most common CNS embryonal tumor accounting for 10-15%-of pediatric CNS tumors.[12] The new WHO CNS5 classification has molecularly divided medulloblastoma (MBL) into four categories (WNT-activated, sonic hedgehog [SHH]-activated TP53 wild-type, SHH-activated TP53-mutant, and non-WNT/non-SHH group that mainly comprises group 3 and 4 lesions) and the previously described histological subtypes are now combined in one category, MBL histologically defined.[22] The other common embryonal tumors are ATRTs and embryonal tumors with multilayered rosettes.

Ependymal and other Pediatric CNS Tumors (WHO I–III)

EP are classified according histopathological/molecular features as well as anatomic site, and are divided into molecular groups across the supratentorial (ZFTA fusion-positive and YAP1 fusion-positive), posterior fossa (two groups PFA and PFB), and spinal compartments (MYCN amplified and myxopapillary EP).[22] The supratentorial EP are associated with calcification and cysts. Leptomeningeal spread can be seen in EP and is not limited to any particular tumor location. The intracranial EP have a significant risk for recurrence and the 5-year overall survival is approximately 50 to 70%.[23]

The most common pituitary tumor in children is CP accounting for 6 to 9%-of pediatric CNS tumors.[24] CP arises from Rathke's pouch remnant and can be sellar or suprasellar and follows the rule of 90% (approximately 90%-have calcification, 90%-are cystic, and 90%-show enhancement). Pituitary microadenoma and macroadenoma are the less common tumors in this category. The adamantinomatous variety of CP is more common in children and papillary variant is more common in adults.

The common pineal tumors are germ cell tumors that can sometimes present as a bifocal tumor and can involve the neurohypophyseal region.[25] Tumor markers show good correlation with different types of germ cell tumors. Calcification is common in pineal tumors. The usual clinical presentation is due to obstructive hydrocephalus due to mass effect on the cerebral aqueduct.

Management of Pediatric CNS Tumors

Surgery, chemotherapy, and radiotherapy (RT) are the main treatment options for pediatric CNS tumors and the choice of treatment depends on the stage of the disease, lesion grade, and anatomical location of the lesion.

Surgery is often the initial treatment choice especially when the tumor is causing significant mass effect or hydrocephalus or raised intracranial pressure. Surgery planning is mostly done on MRI with assistance from other advanced imaging techniques like diffusion-tensor imaging (DTI), functional MRI, and intraoperative monitoring with ultrasonography or intraoperative MRI. Surgery for pediatric CNS tumors is undertaken with curative intent and is extremely valuable in most of the nondiffuse CNS tumors (e.g., medulloblastoma or PA). However, the immediate postoperative MRI (<72>

An extraventricular drain or a ventriculoperitoneal shunt is often required for hydrocephalus and for tumors around the cerebral aqueduct or in the posterior fossa, a third ventriculostomy may be required. For certain tumors like CP, achieving complete resection is often difficult due to its extent and involvement of adjacent structures making surgical debulking a suitable option. However, the CP cysts often fill up and in such cases an Omaya reservoir is inserted to achieve cyst drainage and can also be used for chemotherapy administration.[26]

RT is one of the main treatment modalities for unresectable pediatric CNS tumors and residual disease or for preventing recurrence. Various forms of RT can be used including the conventional photon bean therapy or brachytherapy or the upcoming proton beam therapy. Proton beam therapy is more focused with less complications due to less irradiation of the adjacent uninvolved structures.[27]

Role of chemotherapy in pediatric brain tumors is limited due to poor permeability of chemotherapeutic drugs across the brood–brain barrier; however, it is useful adjunct for certain tumors. Intrathecal chemotherapy is useful for intracranial hemato-lymphoid tumors.

Timing for Imaging

A presurgical baseline MRI brain or spine imaging should be performed for all patients. For patients undergoing surgery, a postoperative MRI scan to assess for residual disease should be performed around 48 hours (within 24–72 hours) as per RAPNO recommendations.[9] [10] This postoperative scan will then be the baseline scan for further imaging follow-up. If only biopsy is performed, then a postbiopsy scan is not required. Follow-up imaging is recommended every 3 months for surveillance in the first year and the interval can be then be slowly increased.[20] [28] In some cases of relapse, follow-up imaging can be performed every 2 months.[10] Approximately 5 to 10%-of pediatric CNS low-grade tumors and 10 to 30%-HGG[29] present with metastasis on presentation or develop secondarily.[30] Thus, spine MRI for brain tumors should be performed at baseline; similarly, baseline brain imaging should be performed for primary spinal cord tumors (SCT). If metastasis is detected, then repeat surveillance MRI of the spine or brain is recommended by the RAPNO committee at the same intervals as the primary tumor site.[9]

NF-1-related low-grade CNS lesions should have similar imaging protocols with additional sequences specific for site, like for orbital imaging ([Supplementary Table S1]).[9] RAPNO has defined the radiological response assessment criteria for pediatric LGG and HGG ([Supplementary Tables S2] and [S3]).

The largest measurable lesion or lesions or the most symptomatic/actively growing lesion should be the target lesion. Measurements are usually done in two or three dimensions and the most reproducible way is to measure the longest dimension in perpendicular planes.[9]

Introduction to Spinal Cord Tumors

SCT are classified based on location as intramedullary (IM), intradural–extramedullary (IDEM), or extradural (ED).[31] Spinal cord neoplasms are comparatively rare. They account for 5 to 10%-of all central nervous system tumors, of which 70 to 80%-are IDEM in location.[32] The intramedullary neoplasms can be glial and nonglial histopathologically. The glial neoplasms include EP, myxopapillary EP, subependymoma, astrocytoma, and ganglioglioma. The nonglial neoplasms include hemangioblastoma, paraganglioma, dermoid, epidermoids, lipomas, hemangiomas, metastasis, and lymphoma.[33] [34] EP are the most commonly seen in adults, while astrocytomas are more common in the pediatric population. The IDEM and ED neoplasms primarily include meningioma and nerve sheath tumors.[32] Other lesions include cysts, metastases, paraganglioma, dermoid, and epidermoids. ED tumors also include the spinal column, of which bone metastasis is the most common.

Etiopathogenesis and Epidemiology

The etiopathogenesis of most primary spinal tumors is unknown. However, exposure to cancer-causing agents may be attributed to some. A genetic role is suspected as these tumors are linked to known inherited syndromes. NF 2 and von Hippel-Lindau disease are the common ones associated with neurofibromas/meningiomas and hemangioblastomas, respectively.

There is scarce data on the incidence of primary SCT. Schellinger et al quoted an overall incidence of spinal cord tumors as 0.74 per 100,000 person-years, with an incidence of 0.77/100,000 in females and 0.70/100,000 in males.[35] Two-third of all spinal tumors are IDEM, and 10%-are IM SCT.[36] According to literature, the primary spinal tumors are more commonly seen in females in the Western population, whereas a slight male preponderance is seen in Asian studies.[37] [38] Male to female ratio of nearly 1.4:1 has been reported in Indian studies.[39] [40] The mean age of presentation of IDEM tumors was 35.8 years, IM was 25.7 years, and ED tumors was 30.7 years.[41] In a study by Chamberlain and Tredway, the mean age of patients with intramedullary spinal cord tumor (IMSCT) was 41 years, which is higher than Indian data.[36]

Clinical Presentation

Back pain, paresthesias, weakness in limbs, and sensory loss are the most frequent presenting symptoms. Scoliosis or other spinal deformities may occur due to weakness of paraspinal muscles when anterior horn cells of the spinal cord are involved. Autonomic dysfunction, including loss of bowel or bladder control and erectile dysfunction may also occur.[40] [42] [43]

Clinical/ Diagnostic Workup Excluding Imaging

A thorough clinical history and examination with a detailed neurological assessment mark the beginning of the assessment. IM tumors have a longer duration of clinical history as compared to IDEM tumors. IDEM tumors commonly have radicular pain, whereas IM tumors present with dull aching pain. Paralysis may occur in different body parts, depending on which level of the spinal cord or corticospinal tracts are involved (distal to proximal muscle weakness occurs in IDEM and proximal to distal weakness in IM tumors). Loss of sensation in the legs, arms, or chest may occur when spinothalamic tracts are involved. Dissociative anesthesia and suspended sensory loss are the classical presentations of IM tumors. Loss of bowel or bladder function occurs earlier in intramedullary tumors than in IDEM tumors. Anterior horn cell involvement, which occurs more commonly in IM tumors, leads to paraspinal muscle wasting causing secondary scoliosis.[40] [42] [43]

Cerebrospinal fluid (CSF) analysis may be considered to assess tumor cells. Laboratory studies are usually not helpful in establishing the diagnosis.

To identify the location and appearance of the tumor, imaging is required in the form of an MRI or CT scan.

Imaging Guidelines

MRI without and with intravenous gadolinium contrast is the modality of choice. It helps differentiate various spinal cord neoplasms; however, the appearances are not always pathognomic.[33] Radiographs and CT scans do not have a role in assessing the primary tumor. They may reveal associated bony changes like scoliosis, widened interpeduncular distance, and bone erosion.[33]

MRI protocol should include T2W sagittal images through the whole spine with tailored down T2 and T1 axials through the area of abnormality. Postcontrast images are at least obtained in sagittal and axial planes with an additional whole spine postcontrast screening to look for additional lesions or drop metastasis. In selected cases, DWI or DTI may be performed.[44] The recommended brain tumor protocol and spinal tumor protocol and metastatic workup imaging evaluation have been described in [Tables 1] and [2], respectively.

References

2. Arora RS, Bagai P, Bhakta N. Estimated national and state level incidence of childhood and adolescent cancer in India. Indian Pediatr 2021; 58 (05) 417-423
3. Jain A, Sharma MC, Suri V. et al. Spectrum of pediatric brain tumors in India: a multi-institutional study. Neurol India 2011; 59 (02) 208-211
4. Kaderali Z, Lamberti-Pasculli M, Rutka JT. The changing epidemiology of paediatric brain tumours: a review from the hospital for sick children. Childs Nerv Syst 2009; 25 (07) 787-793
5. Johnson KJ, Cullen J, Barnholtz-Sloan JS. et al. Childhood brain tumor epidemiology: a brain tumor epidemiology consortium review. Cancer Epidemiol Biomarkers Prev 2014; 23 (12) 2716-2736
6. Patel AP, Fisher JL, Nichols E. et al; GBD 2016 Brain and Other CNS Cancer Collaborators. Global, regional, and national burden of brain and other CNS cancer, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18 (04) 376-393
7. Satyanarayana L, Asthana S, Labani S P. Childhood cancer incidence in India: a review of population-based cancer registries. Indian Pediatr 2014; 51 (03) 218-220
8. Suresh SG, Srinivasan A, Scott JX, Rao SM, Chidambaram B, Chandrasekar S. Profile and outcome of pediatric brain tumors – experience from a tertiary care pediatric oncology unit in South India. J Pediatr Neurosci 2017; 12 (03) 237-244
9. Girardi F, Allemani C, Coleman MP. Worldwide trends in survival from common childhood brain tumors: a systematic review. J Glob Oncol 2019; 5: 1-25
10. Fangusaro J, Witt O, Hernáiz Driever P. et al. Response assessment in paediatric low-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol 2020; 21 (06) e305-e316
11. Erker C, Tamrazi B, Poussaint TY. et al. Response assessment in paediatric high-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol 2020; 21 (06) e317-e329
12. Cooney TM, Cohen KJ, Guimaraes CV. et al. Response assessment in diffuse intrinsic pontine glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol 2020; 21 (06) e330-e336
13. Warren KE, Vezina G, Poussaint TY. et al. Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology committee. Neuro-oncol 2018; 20 (01) 13-23
14. Avula S, Peet A, Morana G, Morgan P, Warmuth-Metz M, Jaspan T. European Society for Paediatric Oncology (SIOPE)-Brain Tumour Imaging Group. European Society for Paediatric Oncology (SIOPE) MRI guidelines for imaging patients with central nervous system tumours. Childs Nerv Syst 2021; 37 (08) 2497-2508
15. Resende LL, Alves CAPF. Imaging of brain tumors in children: the basics-a narrative review. Transl Pediatr 2021; 10 (04) 1138-1168
16. Mata-Mbemba D, Zapotocky M, Laughlin S, Taylor MD, Ramaswamy V, Raybaud C. MRI characteristics of primary tumors and metastatic lesions in molecular subgroups of pediatric medulloblastoma: a single-center study. AJNR Am J Neuroradiol 2018; 39 (05) 949-955
17. Matsusue E, Fink JR, Rockhill JK, Ogawa T, Maravilla KR. Distinction between glioma progression and post-radiation change by combined physiologic MR imaging. Neuroradiology 2010; 52 (04) 297-306
18. Pope WB, Young JR, Ellingson BM. Advances in MRI assessment of gliomas and response to anti-VEGF therapy. Curr Neurol Neurosci Rep 2011; 11 (03) 336-344
19. de Blank P, Bandopadhayay P, Haas-Kogan D, Fouladi M, Fangusaro J. Management of pediatric low-grade glioma. Curr Opin Pediatr 2019; 31 (01) 21-27
20. Sturm D, Pfister SM, Jones DTW. Pediatric gliomas: current concepts on diagnosis, biology, and clinical management. J Clin Oncol 2017; 35 (21) 2370-2377
21. Ater JL, Xia C, Mazewski CM. et al. Nonrandomized comparison of neurofibromatosis type 1 and non-neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low-grade glioma: a report from the Children's Oncology Group. Cancer 2016; 122 (12) 1928-1936
22. Ostrom QT, Gittleman H, Liao P. et al. CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro-oncol 2017; 19 (suppl _5): v1-v88
23. Louis DN, Perry A, Wesseling P. et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-oncol 2021; 23 (08) 1231-1251
24. Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA. Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol 2009; 10 (03) 258-266
25. Drapeau A, Walz PC, Eide JG. et al. Pediatric craniopharyngioma. Childs Nerv Syst 2019; 35 (11) 2133-2145
26. Fujimaki T. Central nervous system germ cell tumors: classification, clinical features, and treatment with a historical overview. J Child Neurol 2009; 24 (11) 1439-1445
27. Zubair A, De Jesus O. Ommaya Reservoir. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2022 Apr 29]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK559011/
28. Rampling R, James A, Papanastassiou V. The present and future management of malignant brain tumours: surgery, radiotherapy, chemotherapy. J Neurol Neurosurg Psychiatry 2004; 75 (Suppl 2): ii24-ii30
29. Ater JL, Zhou T, Holmes E. et al. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group. J Clin Oncol 2012; 30 (21) 2641-2647
30. Benesch M, Wagner S, Berthold F, Wolff JEA. Primary dissemination of high-grade gliomas in children: experiences from four studies of the Pediatric Oncology and Hematology Society of the German Language Group (GPOH). J Neurooncol 2005; 72 (02) 179-183
31. Chalil A, Ramaswamy V. Low grade gliomas in children. J Child Neurol 2016; 31 (04) 517-522
32. Segal D, Lidar Z, Corn A, Constantini S. Delay in diagnosis of primary intradural spinal cord tumors. Surg Neurol Int 2012; 3: 52
33. Koeller KK, Shih RY. Intradural extramedullary spinal neoplasms: radiologic-pathologic correlation. Radiographics 2019; 39 (02) 468-490
34. Koeller KK, Rosenblum RS, Morrison AL. Neoplasms of the spinal cord and filum terminale: radiologic-pathologic correlation. Radiographics 2000; 20 (06) 1721-1749
35. Bansal S, Ailawadhi P, Suri A. et al. Ten years' experience in the management of spinal intramedullary tumors in a single institution. J Clin Neurosci 2013; 20 (02) 292-298
36. Schellinger KA, Propp JM, Villano JL, McCarthy BJ. Descriptive epidemiology of primary spinal cord tumors. J Neurooncol 2008; 87 (02) 173-179
37. Chamberlain MC, Tredway TL. Adult primary intradural spinal cord tumors: a review. Curr Neurol Neurosci Rep 2011; 11 (03) 320-328
38. Wen-qing H, Shi-ju Z, Qing-sheng T. et al. Statistical analysis of central nervous system tumors in China. J Neurosurg 1982; 56 (04) 555-564
39. Hirano K, Imagama S, Sato K. et al. Primary spinal cord tumors: review of 678 surgically treated patients in Japan. A multicenter study. Eur Spine J 2012; 21 (10) 2019-2026
40. Dikondwar AR, Dani AA. Spinal space occupying lesions - pathologic spectrum. J Med Sci Health 2016; 2 (01) 24-29
41. Banga MS, Sandeep BV, Kishan A, Dev AH, Devabhakthuni RB. Spinal cord tumors—our 5-year experience. Indian Journal of Neurosurgery 2022
42. Arora RK, Kumar R. Spinal tumors: trends from Northern India. Asian J Neurosurg 2015; 10 (04) 291-297
43. Engelhard HH, Villano JL, Porter KR. et al. Clinical presentation, histology, and treatment in 430 patients with primary tumors of the spinal cord, spinal meninges, or cauda equina. J Neurosurg Spine 2010; 13 (01) 67-77
44. Narayan S, Rege SV, Gupta R. Clinicopathological study of intradural extramedullary spinal tumors and its correlation with functional outcome. Cureus 2021; 13 (06) e15733
45. Shih RY, Koeller KK. Intramedullary masses of the spinal cord: radiologic-pathologic correlation. Radiographics 2020; 40 (04) 1125-1145
46. Scibilia A, Terranova C, Rizzo V. et al. Intraoperative neurophysiological mapping and monitoring in spinal tumor surgery: sirens or indispensable tools?. Neurosurg Focus 2016; 41 (02) E18
47. Coronel EE, Lien RJ, Ortiz AO. Postoperative spine imaging in cancer patients. Neuroimaging Clin N Am 2014; 24 (02) 327-335

    Address for correspondence

    Abhishek Mahajan, MD, MRes, FRCR (UK)
    Department of Radiology, The Clatterbridge Cancer Centre NHS Foundation Trust
    Pembroke Place, Liverpool, L7 8YA
    United Kingdom   
    Email: drabhishek.mahajan@yahoo.in
    
    

    Publication History

    Article published online:
    06 March 2023
    

    © 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

    Thieme Medical and Scientific Publishers Pvt. Ltd.
    A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

    
    

    We recommend

    1. Transition of Care for Children with High-Grade Central Nervous System Tumors
       Yosef Ellenbogen et al., VCOT Open
    2. Profile of Primary Pediatric Brain and Spinal Cord Tumors from North India
       Nadia Shirazi et al., Indian Journal of Medical and Paediatric Oncology, 2017
    3. Demographic and histopathologic profile of pediatric brain tumors: A hospital-based study
       Harshil C. Shah et al., South Asian Journal of Cancer, 2015
    4. Current Management of Pediatric Brain Tumors
       Ian F. Pollack et al., Seminars in Neurosurgery, 2002
    5. Demographic and Histopathologic Profile of Pediatric Patients with Primary Brain Tumors Attending a Regional Cancer Center
       Dhruv Pankaj Mehta et al., Indian Journal of Medical and Paediatric Oncology, 2019
    1. Advances in neuroimaging studies of alcohol use disorder (AUD) 
       Ji-Yu Xie et al., Psychoradiology, 2022
    2. Scanning reproducible brain-wide associations: sample size is all you need?
       Xiang-Zhen Kong et al., Psychoradiology, 2022
    3. Massive health industry urgently needs to be guided by project management theory
       Yi Mou et al., History & Philosophy of Medicine, 2021
    4. Massive health industry urgently needs to be guided by project management theory
       Yi Mou et al., History & Philosophy of Medicine, 2021
    5. Clinical Diabetes CME Series: Anemia in Chronic Kidney Disease in Primary Care
       Stephen Brunton et al, Clinical Diabetes

References

2. Arora RS, Bagai P, Bhakta N. Estimated national and state level incidence of childhood and adolescent cancer in India. Indian Pediatr 2021; 58 (05) 417-423
3. Jain A, Sharma MC, Suri V. et al. Spectrum of pediatric brain tumors in India: a multi-institutional study. Neurol India 2011; 59 (02) 208-211
4. Kaderali Z, Lamberti-Pasculli M, Rutka JT. The changing epidemiology of paediatric brain tumours: a review from the hospital for sick children. Childs Nerv Syst 2009; 25 (07) 787-793
5. Johnson KJ, Cullen J, Barnholtz-Sloan JS. et al. Childhood brain tumor epidemiology: a brain tumor epidemiology consortium review. Cancer Epidemiol Biomarkers Prev 2014; 23 (12) 2716-2736
6. Patel AP, Fisher JL, Nichols E. et al; GBD 2016 Brain and Other CNS Cancer Collaborators. Global, regional, and national burden of brain and other CNS cancer, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18 (04) 376-393
7. Satyanarayana L, Asthana S, Labani S P. Childhood cancer incidence in India: a review of population-based cancer registries. Indian Pediatr 2014; 51 (03) 218-220
8. Suresh SG, Srinivasan A, Scott JX, Rao SM, Chidambaram B, Chandrasekar S. Profile and outcome of pediatric brain tumors – experience from a tertiary care pediatric oncology unit in South India. J Pediatr Neurosci 2017; 12 (03) 237-244
9. Girardi F, Allemani C, Coleman MP. Worldwide trends in survival from common childhood brain tumors: a systematic review. J Glob Oncol 2019; 5: 1-25
10. Fangusaro J, Witt O, Hernáiz Driever P. et al. Response assessment in paediatric low-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol 2020; 21 (06) e305-e316
11. Erker C, Tamrazi B, Poussaint TY. et al. Response assessment in paediatric high-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol 2020; 21 (06) e317-e329
12. Cooney TM, Cohen KJ, Guimaraes CV. et al. Response assessment in diffuse intrinsic pontine glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol 2020; 21 (06) e330-e336
13. Warren KE, Vezina G, Poussaint TY. et al. Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology committee. Neuro-oncol 2018; 20 (01) 13-23
14. Avula S, Peet A, Morana G, Morgan P, Warmuth-Metz M, Jaspan T. European Society for Paediatric Oncology (SIOPE)-Brain Tumour Imaging Group. European Society for Paediatric Oncology (SIOPE) MRI guidelines for imaging patients with central nervous system tumours. Childs Nerv Syst 2021; 37 (08) 2497-2508
15. Resende LL, Alves CAPF. Imaging of brain tumors in children: the basics-a narrative review. Transl Pediatr 2021; 10 (04) 1138-1168
16. Mata-Mbemba D, Zapotocky M, Laughlin S, Taylor MD, Ramaswamy V, Raybaud C. MRI characteristics of primary tumors and metastatic lesions in molecular subgroups of pediatric medulloblastoma: a single-center study. AJNR Am J Neuroradiol 2018; 39 (05) 949-955
17. Matsusue E, Fink JR, Rockhill JK, Ogawa T, Maravilla KR. Distinction between glioma progression and post-radiation change by combined physiologic MR imaging. Neuroradiology 2010; 52 (04) 297-306
18. Pope WB, Young JR, Ellingson BM. Advances in MRI assessment of gliomas and response to anti-VEGF therapy. Curr Neurol Neurosci Rep 2011; 11 (03) 336-344
19. de Blank P, Bandopadhayay P, Haas-Kogan D, Fouladi M, Fangusaro J. Management of pediatric low-grade glioma. Curr Opin Pediatr 2019; 31 (01) 21-27
20. Sturm D, Pfister SM, Jones DTW. Pediatric gliomas: current concepts on diagnosis, biology, and clinical management. J Clin Oncol 2017; 35 (21) 2370-2377
21. Ater JL, Xia C, Mazewski CM. et al. Nonrandomized comparison of neurofibromatosis type 1 and non-neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low-grade glioma: a report from the Children's Oncology Group. Cancer 2016; 122 (12) 1928-1936
22. Ostrom QT, Gittleman H, Liao P. et al. CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro-oncol 2017; 19 (suppl _5): v1-v88
23. Louis DN, Perry A, Wesseling P. et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-oncol 2021; 23 (08) 1231-1251
24. Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA. Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol 2009; 10 (03) 258-266
25. Drapeau A, Walz PC, Eide JG. et al. Pediatric craniopharyngioma. Childs Nerv Syst 2019; 35 (11) 2133-2145
26. Fujimaki T. Central nervous system germ cell tumors: classification, clinical features, and treatment with a historical overview. J Child Neurol 2009; 24 (11) 1439-1445
27. Zubair A, De Jesus O. Ommaya Reservoir. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2022 Apr 29]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK559011/
28. Rampling R, James A, Papanastassiou V. The present and future management of malignant brain tumours: surgery, radiotherapy, chemotherapy. J Neurol Neurosurg Psychiatry 2004; 75 (Suppl 2): ii24-ii30
29. Ater JL, Zhou T, Holmes E. et al. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group. J Clin Oncol 2012; 30 (21) 2641-2647
30. Benesch M, Wagner S, Berthold F, Wolff JEA. Primary dissemination of high-grade gliomas in children: experiences from four studies of the Pediatric Oncology and Hematology Society of the German Language Group (GPOH). J Neurooncol 2005; 72 (02) 179-183
31. Chalil A, Ramaswamy V. Low grade gliomas in children. J Child Neurol 2016; 31 (04) 517-522
32. Segal D, Lidar Z, Corn A, Constantini S. Delay in diagnosis of primary intradural spinal cord tumors. Surg Neurol Int 2012; 3: 52
33. Koeller KK, Shih RY. Intradural extramedullary spinal neoplasms: radiologic-pathologic correlation. Radiographics 2019; 39 (02) 468-490
34. Koeller KK, Rosenblum RS, Morrison AL. Neoplasms of the spinal cord and filum terminale: radiologic-pathologic correlation. Radiographics 2000; 20 (06) 1721-1749
35. Bansal S, Ailawadhi P, Suri A. et al. Ten years' experience in the management of spinal intramedullary tumors in a single institution. J Clin Neurosci 2013; 20 (02) 292-298
36. Schellinger KA, Propp JM, Villano JL, McCarthy BJ. Descriptive epidemiology of primary spinal cord tumors. J Neurooncol 2008; 87 (02) 173-179
37. Chamberlain MC, Tredway TL. Adult primary intradural spinal cord tumors: a review. Curr Neurol Neurosci Rep 2011; 11 (03) 320-328
38. Wen-qing H, Shi-ju Z, Qing-sheng T. et al. Statistical analysis of central nervous system tumors in China. J Neurosurg 1982; 56 (04) 555-564
39. Hirano K, Imagama S, Sato K. et al. Primary spinal cord tumors: review of 678 surgically treated patients in Japan. A multicenter study. Eur Spine J 2012; 21 (10) 2019-2026
40. Dikondwar AR, Dani AA. Spinal space occupying lesions - pathologic spectrum. J Med Sci Health 2016; 2 (01) 24-29
41. Banga MS, Sandeep BV, Kishan A, Dev AH, Devabhakthuni RB. Spinal cord tumors—our 5-year experience. Indian Journal of Neurosurgery 2022
42. Arora RK, Kumar R. Spinal tumors: trends from Northern India. Asian J Neurosurg 2015; 10 (04) 291-297
43. Engelhard HH, Villano JL, Porter KR. et al. Clinical presentation, histology, and treatment in 430 patients with primary tumors of the spinal cord, spinal meninges, or cauda equina. J Neurosurg Spine 2010; 13 (01) 67-77
44. Narayan S, Rege SV, Gupta R. Clinicopathological study of intradural extramedullary spinal tumors and its correlation with functional outcome. Cureus 2021; 13 (06) e15733
45. Shih RY, Koeller KK. Intramedullary masses of the spinal cord: radiologic-pathologic correlation. Radiographics 2020; 40 (04) 1125-1145
46. Scibilia A, Terranova C, Rizzo V. et al. Intraoperative neurophysiological mapping and monitoring in spinal tumor surgery: sirens or indispensable tools?. Neurosurg Focus 2016; 41 (02) E18
47. Coronel EE, Lien RJ, Ortiz AO. Postoperative spine imaging in cancer patients. Neuroimaging Clin N Am 2014; 24 (02) 327-335